INS and Insulin resistance: IRS1 phosphorylation at Ser636/639 and Ser307 inhibits IRS1 binding to IR and elevated levels of phosphorylation of serine/threonine in IRS1 reduce IRS1 affinity with the p85 regulatory subunit of PI3K, weakening insulin signal transduction and leading to the symptom of insulin resistance, according to studies [102, 103].